微流控技术研究若干进展

微流控芯片(又称芯片实验室)是一种以在微米尺度空间对流体进行操控为主要特征的科学技术。它具有将化学和生物实验室的基本 功能微缩到一个几平方厘米芯片上的能力,已经显示了重要的应用前景。作为一种新兴的科学技术,微流控研究已经涉及化学、生物 学、工程学和物理学等诸多领域,学科交叉性强,分析化学则是其第一轮也是最直接的一个应用领域。近年来,微流控研究发展迅速, 技术创新层出不穷,应用领域不断拓宽。本文仅以近期发表在本领域主要国际刊物的几个工作为典型案例,介绍微流控技术研究的若 干进展。     

微流控技术在生命分析化学中的应用进展

微流控分析系统与宏观条件下的分析体系相比,具有样品和试剂消耗小、传质传热效率高、生物相容性较好、高通量并行分析、功能单元集成化、微型化及自动化控制等特点,在分析化学尤其是生命分析化学领域得到了广泛应用。本文以涉及细胞的微流控技术为切入点,主要介绍了近五年来微流控芯片相关技术的发展,如芯片材料与制作技术、表面改性技术和液滴技术等,并简单总结微流控技术在药物筛选和细胞分析等生命分析化学领域的研究应用进展。     

微系统科技的发展及电化学的新应用

本文根据田昭武在中国化学会第一届全国纳米技术与应用会议 (2 0 0 0 .11.2 8,厦门 )特邀大会报告内容整理而成 :1　微系统技术概述 (技术的必要性和前景 )2　发展微系统技术的特殊困难3　电化学在微系统技术中的应用　 3.1　用于复杂 3D 图形微加工的约束刻蚀剂层技术 (CELT)　 3.2　聚焦电泳和微系统在 (生物 )化学中的应用 (μ TAS或芯片上实验室 )　 3.3　芯片实验室中微流体输运网络的合理选择之一 -灵巧 (Smart)电渗泵4　结论     

电分析化学国家重点实验室脱颖而出

不久前,国家科技部组织专家组对长春应用化学研究所电分析国家重点实验室建设进行了现场验收,专家组对该实验室的科研工作、人才培养和仪器装备建设情况进行了实地考察,一致认为达到了国家重点实验室建设目标,取得了显著成绩。 该实验室于2001年7月经国家科技部批准,在原已建立十余年的中国科学院电分析化学开放研究实验室的基础上建设而成。该实验室立足世界电分析化学发展前沿,在电分析化学领域应用基础研究方面,承担了国家“十五”科技     

光子晶体在分析化学中的应用

光子晶体是一新兴的光学材料,正越来越多地应用于分析化学领域,有可能成为新的研究热点。本文着重介绍与分析化学相关的光子晶体研究,特别关注其在色谱、毛细管与芯片电泳等分离分析方面的应用。     

微流控技术研究的若干进展

微流控芯片(又称芯片实验室)是一种以在微米尺度空间对流体进行操控为主要特征的科学技术。它具有将化学和生物实验室的基本功能微缩到一个几平方厘米芯片上的能力,已经显示了重要的应用前景。作为     

2002年欧洲出版的分析化学新刊介绍

1　《芯片上的实验室》(Ｌａｂｏｎａｃｈｉｐ)《芯片上的实验室》由联合王国皇家化学会出版。 2 0 0 1年试刊两期 ,2 0 0 2年正式出版季刊。内容涉及合成化学、生物工艺、电子学、分析化学、环境监测、药物筛选、医学诊断、临床化学、药物材料科学、工程学、流体学、研究废物最少化、反应器工艺和制作、机器人学、组合化学、基因组学、蛋白组学、细胞组学等。重点报道有机合成和生物学合成、生物 免疫分析、聚合物微制作、生物学矩阵微型加工、催化(生物学 )、脱氧核糖核酸测序和分子诊断学、微型化学反应器件和工艺、聚合酶链式反应、微型…     

关于举办《第五届国际电分析化学研讨会》的通知

《第五届国际电分析化学研讨会》由中国化学会分析化学委员会主办,委托中科院长春应用化学研究所电分析化学开放研究实验室举办,研讨会将于1995年10月20日至23日在长春应化所举行.研讨会将特邀20多名国际著名电分析化学家参加,会议主要语言为英语.欲参加研讨会的同志(如提出报告请交中、英文摘要各一份,每份不超过一页)请速在1995年6月30日前与长春斯大林大街109号中科院长春应化所电分析化学开放研究实验室(邮政编码 130022)(传真号0431—5685653)朱果逸联系,随后寄上第二轮通知.     

关于举办《第五届国际电分析化学研讨会》的通知

《第五届国际电分析化学研讨会》由中国化学会分析化学委员会主办,委托中科院长春应用化学研究所电分析化学开放研究实验室举办,研讨会将于1995年10月20日至23日在长春应化所举行.研讨会将特邀20多名国际著名电分析化学家参加,会议主要语言为英语.钦参加研讨会的同志(如提出报告请交中、英文摘要各一份,每份不超过一页)请速在1995年6月30日前与长春斯大林大街109号中科院长春应化所电分析化学开放研究实验室(邮政编码130022)(传真号0431—5685653)朱果逸联系,随后寄上第二轮通知.     

分析化学实验室手册

本书是一本利于实验室工作的手册,但它又远远超越了实验室范畴,可以说是一本浓缩版分析化学百科全书,涵盖分析化学基础、分析测试仪器、实验操作技能和常用数据资料。可供广大实验室分析检测工作者、分析化学研究人员阅读和参考,还可供高等院校相关专业师生参考。     

Analysis Laboratory on a Chip

Microfluidic chip offers a promising platform for chemical or biological analysis on the basis of flexible integration of various functional operation units. This article provides an overview of the recent achievements of microfluidic chip and its applications based on the works mainly carried out in the authors' lab, especially for the purpose of constructing analytical laboratory on a microfluidic chip. Different operation units and some representative applications in molecules, cell and organism analysis are described.     

一种可绝对定量核酸的数字PCR微流控芯片

构建了一种新型的可进行核酸单分子扩增和核酸绝对定量的数字聚合酶链式反应(数字PCR)微流控芯片. 应用多层软光刻技术, 以聚二甲基硅氧烷(PDMS)作为芯片材料, 盖玻片作为基底制作了具有3层结构以及微阀控制功能的微流控芯片. 芯片的大小与载玻片相当, 可同时检测4个样品, 每个样品通入芯片后平均分配到640个反应小室, 每个小室的体积为6 nL. 以从肺癌细胞A549中提取的18sRNA为样品检测了该芯片的可行性. 将样品稀释数倍后通入芯片, 核酸分子随机分布在640个小室中并扩增. 核酸分子在芯片中的分布符合泊松分布原理, 当样品中待测核酸分子平均拷贝数低于0.5个/小室时, 则每个反应小室包含0个或1个分子. 经过PCR扩增后, 有模板分子的小室检测结果为阳性反应, 而无模板分子的小室为阴性反应, 最后通过计数阳性反应室的个数, 可绝对定量原始待测样品中的目标DNA分子拷贝数. 实验结果表明, 该数字 PCR芯片可实现DNA单分子反应和核酸绝对定量, 具有成本低、 灵敏度高、 节省时间和试剂以及操作简单等优点, 为数字PCR方法在普通实验室的应用提供了一种新途径, 可用于癌症及感染性疾病的早期诊断、 单细胞分析、 产前诊断以及各种细菌病毒的核酸检验等研究.     

Approaching absolute zero

We start with a brief background to the field of ultracold atoms and degenerate quantum gases and then review research in this field currently in progress in our laboratory in Melbourne. Current experiments include the use of a permanent magnetic film atom chip to create a Bose–Einstein condensate (BEC) of ⁸⁷Rb atoms; the use of a periodic magnetic microstructure on an atom chip to produce a magnetic lattice for trapping ultracold atoms and BECs; and the production of a BEC of ⁶Li₂ molecules, comprising pairs of weakly bound fermionic ⁶Li atoms, and a degenerate Fermi gas of ⁶Li atoms in an optical dipole trap near a Feshbach resonance.     

Quantitative measurement of serum allergen-specific IgE on protein chip

Type I allergy is an immunoglobulin E (IgE)-mediated hypersensitivity disease inflicting more than quarter of the world population. In order to identify allergen sources, skin provocation test and IgE serology was performed using allergen extracts. Such process identifies allergen-containing sources but cannot identify the disease-eliciting allergenic molecules. Recently, microarray technology has been developed for allergen-specific IgE detection using rolling circle amplification. This study was carried out to evaluate protein chip technology for the quantitative measurement and limits of sensitivity of multiple allergen-specific IgE by an immunofluorescence assay. Significance of positive calibrators was tested using purified human IgE. Dermatophagoides pteronyssinus (Dp), egg white, milk, soybean, and wheat were used as allergens and human serum albumin as negative control. Sensitivity and clinical efficacy of protein chip were evaluated using allergy immune serum for Dp. The fluorescent intensities for purified human IgE as calibrator were well correlated with the concentrations of human IgE. Two-fold dilution of serum allowed an optimal reaction with Dp (1 mg/ml) at which serum Dp-specific IgE levels by protein chip were compatible with those by UniCap. The sensitivity of protein chip in this study was found at level of 1 IU/ml of IgE. Dp-specific IgE levels by protein chip correlated well with those of UniCap by comparing 10 atopic dermatitis. Additional 18 sera were tested for above multiple antigens other than Dp and significant results were obtained for many antigens as well as Dp. These results indicated that spotting of heterogeneous protein mixture on protein chip and the quantitative measurement of serum allergen-specific IgE levels using immunofluorescence assay can be successfully applied in the clinical laboratory for the diagnosis of allergy and could be applied to diagnosis of autoimmune and infectious diseases     

Nano‐Porous Light‐Emitting Silicon Chip as a Potential Biosensor Platform

Abstract

Nano‐porous silicon (PS) offers a potential platform for biosensors with benefits both in terms of light emission and the large functional surface area. A light emitting PS chip with a stable and functional surface was fabricated in our laboratory. When protein was deposited on it, the light emission was reduced in proportion to the protein concentration. Based on this property, we developed a rudimentary demonstration of a label‐free sensor to detect bovine serum albumin (BSA). A serial concentration of BSA was applied to the light chip and the reduction in light emission was measured. The reduction of the light intensity was linearly related to the concentration of the BSA at concentrations below 10^?5 M. The detection limit was 8×10^?9 M.     

Monitoring on-chip Pictet-Spengler reactions by integrated analytical separation and label-free time-resolved fluorescence

High-throughput screening for optimal reaction conditions and the search for efficient catalysts is of eminent importance in the development of chemical processes and for expanding the spectrum of synthetic methodologies in chemistry. In this context we report a novel approach for a microfluidic chemical laboratory integrating organic synthesis, separation and time-resolved fluorescence detection on a single microchip. The feasibility of our integrated laboratory is demonstrated by monitoring the formation of tetrahydroisoquinoline derivatives by Pictet-Spengler condensation. After on-chip reaction the products and residual starting material were separated enantioselectively on the same chip. On-chip deep UV laser-induced fluorescence detection with time-correlated single photon counting was applied for compound assignment. The system was utilized to screen reaction conditions and various substrates for Pictet-Spengler reactions on-chip. Finally, the microlab was successfully applied to investigate enantioselective reactions using BINOL-based phosphoric acids as organocatalysts.     

Microchip separations of protein biotoxins using an integrated hand-held device

We report the development of a hand-held instrument capable of performing two simultaneous microchip separations (gel and zone electrophoresis), and demonstrate this instrument for the detection of protein biotoxins. Two orthogonal analysis methods are chosen over a single method in order to improve the probability of positive identification of the biotoxin in an unknown mixture. Separations are performed on a single fused-silica wafer containing two separation channels. The chip is housed in a microfluidic manifold that utilizes o-ring sealed fittings to enable facile and reproducible fluidic connection to the chip. Sample is introduced by syringe injection into a septum-sealed port on the device exterior that connects to a sample loop etched onto the chip. Detection of low nanomolar concentrations of fluorescamine-labeled proteins is achieved using a miniaturized laser-induced fluorescence detection module employing two diode lasers, one per separation channel. Independently controlled miniature high-voltage power supplies enable fully programmable electrokinetic sample injection and analysis. As a demonstration of the portability of this instrument, we evaluated its performance in a laboratory field test at the Defence Science and Technology Laboratory with a series of biotoxin variants. The two separation methods cleanly distinguish between members of a biotoxin test set. Analysis of naturally occurring variants of ricin and two closely related staphylococcal enterotoxins indicates the two methods can be used to readily identify ricin in its different forms and can discriminate between two enterotoxin isoforms.     

Feedback control system simulator for the control of biological cells in microfluidic cross slots and integrated microfluidic systems

Control systems for lab on chip devices require careful characterisation and design for optimal performance. Traditionally, this involves either extremely computationally expensive simulations or lengthy iteration of laboratory experiments, prototype design, and manufacture. In this paper, an efficient control simulation technique, valid for typical microchannels, Computed Interpolated Flow Hydrodynamics (CIFH), is described that is over 500 times faster than conventional time integration techniques. CIFH is a hybrid approach, utilising a combination of pre-computed flows and hydrodynamic equations and allows the efficient simulation of dynamic control systems for the transport of cells through micro-fluidic devices. The speed-ups achieved by using pre-computed CFD solutions mapped to an n-dimensional control parameter space, significantly accelerate the evaluation and improvement of control strategies and chip design. Here, control strategies for a naturally unstable device geometry, the microfluidic cross-slot, have been simulated and optimal parameters have been found for proposed devices capable of trapping and sorting cells.     

A Rotary Polydimethylsiloxane‐Based Device for Polymerase Chain Reaction

Abstract

A novel rotary channel polymerase chain reaction (PCR) microchip with polydimethylsiloxane (PDMS) is developed in our laboratory. The chip circular platinum thin‐film heaters and thermometers. Compared with other continuous‐flow PCR chips, the novel rotary channel and the circular heating arrangements in this chip make the loaded reagent mixture pass through three constant‐temperature zones in a very direct sequence, which avoids a melted sample's subjection to the extension temperature before reaching the annealing zone and improves the PCR yield effectively. Several experiments are performed to verify the ability of the device. The results show that the device achieves 25 cycles in 35 min with flow rate 3 µl/min compared to about 45 min in a standard batch PCR system.     

Chemiluminometric enzyme-linked immunosorbent assays (ELISA)-on-a-chip biosensor based on cross-flow chromatography

A chemiluminometric biosensor system for point-of-care testing has been developed using an immuno-chromatographic assay combined with an enzyme (e.g., horseradish peroxidase) tracer that produces a light signal measurable on a simple detector. Cross-flow chromatography, a method previously investigated by our laboratory, was utilized in order to accomplish sequential antigen-antibody binding and signal generation. This enzyme-linked immunosorbent assay (ELISA) was effectively carried out on a plastic chip that was redesigned to simplify the fabrication process. To enhance the sensitivity, biotin-streptavidin capture technology was employed in preparing an immuno-strip that was then incorporated onto the chip in order to generate the ELISA-on-a-chip (EOC) biosensor. Samples containing cardiac troponin I (cTnI) were analyzed using the EOC. A chemiluminescent signal proportional to the analyte concentration was produced by adding a luminogenic substrate to the tracer enzyme complexed with the analyte on the chip. The luminescent signal was detected in a dark chamber mounted with a cooled charge-coupled device and the signal was converted to optical density for quantification. This EOC biosensor system was capable of detecting cTnI present in serum at concentrations as low as 0.027 ng mL⁻¹, 30 times lower than those measured using the conventional rapid test kit with colloidal gold as the tracer. In addition, the final data was acquired within 30 s after the addition of the enzyme substrate, which was faster than the detection time required when using a colorimetric substrate with the same tracer enzyme.